Chronic antidepressant treatments increase cytochrome b mRNA levels in mouse cerebral cortex.
Antidepressant therapies include drugs with a remarkable structural diversity and non-pharmacological interventions, such as electroconvulsive shock. Although the primary neurochemical effects of these treatments may differ, the > or = 2- to 3-wk lag in therapeutic onset has led to the hypothesis that adaptive changes in a final common pathway are required for an antidepressant action. Based on this hypothesis, we sought to identify and characterize common changes in gene expression following chronic antidepressant treatments. We utilized a differential display strategy to identify genes that were differentially expressed in mice following chronic treatment with imipramine and electroconvulsive shock. Differential display PCR followed by subcloning, screening by reverse Northern blot, and confirmation by Northern blot revealed a significant increase in the expression of one gene candidate from mouse cortex following antidepressant treatments. The sequence of this 193-bp gene candidate was an exact match to the DNA sequence of mouse mitochondrial cytochrome b. In contrast to the increased mRNA levels of cytochrome b found in cortex, chronic treatment with these antidepressants did not alter mRNA levels in hippocampus, cerebellum, or liver. Moreover, no differences in cortical levels of cytochrome b mRNA were observed after either acute antidepressant treatments or chronic treatment with nonantidepressant drugs (haloperidol and morphine). The observation that chronic, but not acute treatment with imipramine and electroconvulsive shock produces a region-specific change in the levels of mRNA encoding cytochrome b suggests that this enzyme may be involved in the sequence of events resulting in an antidepressant action.
Huang
N Y
NY
Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
Strakhova
M
M
Layer
R T
RT
Skolnick
P
P
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003573:Cytochrome b Group / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D004334:Drug Administration Schedule; D004597:Electroshock / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000008:administration & dosage; D007099:Imipramine / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism
D000928:Antidepressive Agents; D003573:Cytochrome b Group; D012333:RNA, Messenger; D009020:Morphine; D006220:Haloperidol; D007099:Imipramine